YH001 + Envafolimab for Sarcoma

Not currently recruiting at 5 trial locations

Overseen By James Freddo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Tracon Pharmaceuticals Inc.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: GIST, Desmoid tumors, Coronary syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for individuals with advanced or metastatic sarcoma, a type of cancer. Researchers aim to assess the effectiveness and safety of combining YH001 and envafolimab (an immune checkpoint inhibitor), with the occasional addition of doxorubicin, a common cancer drug. The study divides participants into groups to test these combinations on different sarcoma subtypes. It suits those with advanced sarcoma who have not responded to standard treatments and have not yet tried immune checkpoint inhibitors or doxorubicin. Participants must have sarcoma confirmed by a doctor and measurable tumors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic corticosteroids or other immunosuppressive medications within 14 days before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of treatments YH001 and envafolimab, with or without doxorubicin, is being tested for safety in patients. Previous studies have found that most people can handle the side effects of this combination. However, some serious side effects have been reported. For example, 19% of patients on a similar treatment, nivolumab, and 26% on another treatment experienced significant side effects. While many can tolerate the treatment, some may have serious side effects. Discussing these details with a doctor is important before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about YH001 and Envafolimab for treating sarcoma because they work differently from traditional options like surgery, radiation, and chemotherapy. Most sarcoma treatments rely on these methods to remove or destroy cancer cells, but YH001 and Envafolimab target the immune system, enhancing the body's natural ability to fight cancer. Envafolimab is a novel PD-L1 inhibitor delivered subcutaneously, which may offer more convenience and potentially fewer side effects compared to intravenous infusions. YH001 is a new anti-CTLA-4 antibody, aiming to boost the immune response even further. This innovative approach could provide new hope for patients, especially those with aggressive or treatment-resistant sarcoma subtypes.

What evidence suggests that this trial's treatments could be effective for sarcoma?

Research has shown that combining the drugs YH001 and envafolimab may help treat sarcoma, a type of cancer. Early studies suggest these drugs can work together to help the immune system attack cancer cells. In this trial, some participants will receive YH001 and envafolimab alone, while others will receive these drugs combined with doxorubicin, a chemotherapy drug. Envafolimab helps the immune system fight cancer more effectively, and YH001 is being tested to see if it can further boost this immune response. Early results indicate that when used with doxorubicin, these drugs may work better against advanced sarcoma. Although more research is needed, these combinations show promise in effectively targeting sarcoma. ^{1 2 3 5 6}

Who Is on the Research Team?

James Freddo, MD

Principal Investigator

Medical Monitor

Are You a Good Fit for This Trial?

Adults with advanced or metastatic sarcoma, except for UPS or MFS types, who haven't had immune checkpoint inhibitors or doxorubicin. They should have measurable disease and good organ function. Women must not be pregnant and agree to birth control; men must use a condom if not sterile.

Inclusion Criteria

I am willing and able to give my consent to participate in the study.

I am either not able to have children due to surgery or a medical condition, or I can have children but agree to use birth control.

My organs are working well.

Exclusion Criteria

I haven't taken steroids or immunosuppressants in the last 14 days.

Known allergy to any component of any study drug that the patient would receive if enrolled into this study

I have not had a heart attack or other serious heart problems in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

YH001 is given in combination with envafolimab, and then with envafolimab plus doxorubicin every 3 weeks

8 months

Visits every 3 weeks

Phase 2 Treatment

YH001 is given in combination with envafolimab, with or without doxorubicin, in patients with select histologies of advanced or metastatic sarcoma

22 months

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Doxorubicin
• Envafolimab
• YH001

Trial Overview The study is testing YH001 in combination with Envafolimab, and then adding Doxorubicin for certain patients. It's an open-label trial meaning everyone knows what treatment they're getting, starting with Phase 1/2 followed by specific patient groups in Phase 2.

How Is the Trial Designed?

Group I: P2: Sarcoma Subtype 4 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses

Group II: P2: Sarcoma Subtype 3 RP2D YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks and Doxorubicin every 3 weeks for a maximum of 6 doses

Group III: P2: Sarcoma Subtype 2 RP2D YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks

Group IV: P2: Sarcoma Subtype 1 RP2D YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Recommended Phase 2 Dose of YH001 in combination with Dose 1 of Envafolimab every 3 weeks

Group V: P1 Cohort 2B: Dose 2 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.

Group VI: P1 Cohort 2A: Dose 2 YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.

Group VII: P1 Cohort 1B: Dose 1 YH001 + Dose 1 Envafolimab + Doxorubicin Q3WK Experimental Treatment 3 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 of Envafolimab with Doxorubicin every 3 weeks.

Group VIII: P1 Cohort 1A: Dose 1 YH001 + Dose 1 Envafolimab Q3WK Experimental Treatment 2 Interventions

Dose 1 of YH001 will be dosed in combination with Dose 1 Envafolimab every 3 weeks.

Who Is Running the Clinical Trial?

Tracon Pharmaceuticals Inc.

Lead Sponsor

Trials

22

Recruited

1,000+

Published Research Related to This Trial

In a phase 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free survival rate of 49% at 12 weeks, indicating its potential efficacy as a treatment option.

While the treatment was generally active, it was associated with some serious adverse events, including one case of grade 5 pneumonitis and colitis, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Somaiah, N., Conley, AP., Parra, ER., et al.[2023]

In a phase 2 study involving 85 patients with metastatic sarcoma, the combination of nivolumab and ipilimumab showed a higher confirmed response rate (16%) compared to nivolumab alone (5%), indicating that the combination therapy may be more effective for certain sarcoma subtypes.

While both treatments had manageable safety profiles, serious treatment-related adverse events occurred in 19% of patients receiving nivolumab and 26% in those receiving the combination therapy, suggesting that while the combination is promising, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. D'Angelo, SP., Mahoney, MR., Van Tine, BA., et al.[2021]

Envafolimab, the first subcutaneously injectable PD-L1 antibody, was well tolerated in a Phase 1 trial with 35 Japanese patients, showing no dose-limiting toxicities and a safety profile similar to existing treatments.

The overall response rate was 11.4% and the disease control rate was 34.3%, indicating that envafolimab is effective and offers a more convenient dosing schedule compared to traditional intravenous PD-1/PD-L1 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors. Shimizu, T., Nakajima, TE., Yamamoto, N., et al.[2022]

The combination of the mTOR inhibitor nab-sirolimus and the immune checkpoint inhibitor nivolumab was found to be safe for patients with advanced sarcoma, with a maximum-tolerated dose established at 100 mg/m2 and no unexpected adverse events reported.

While the treatment did not improve overall outcomes compared to nivolumab alone, the best responses were observed in patients with specific genetic mutations, such as PTEN loss and TSC2 mutation, indicating potential for biomarker-driven approaches in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Investigation of Safety and Efficacy of Nivolumab and nab-Sirolimus in Patients With a Variety of Tumors With Genetic Mutations in the mTOR Pathway. Gordon, EM., Angel, NL., Omelchenko, N., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05448820

YH001 Plus Envafolimab With or Without Doxorubicin in ... This is a multicenter, open label, Phase 1/2 study of YH001 initially given in combination with envafolimab, and then given in combination with envafolimab ...

2. clin.larvol.com clin.larvol.com/trial-detail/NCT05448820

YH001 Plus Envafolimab With or Without Doxorubicin in ... The Phase 1/2 trial will assess the safety and efficacy of the triplet combination of YH001, envafolimab and doxorubicin in the common sarcoma subtypes of ...

3. biospace.com biospace.com/tracon-pharmaceuticals-announces-dosing-of-first-patient-in-phase-1-2-trial-of-yh001-in-combination-with-envafolimab-and-doxorubicin-in-front-line-sarcoma

TRACON Pharmaceuticals Announces Dosing of First ... The Phase 1/2 trial will assess the safety and efficacy of the triplet combination of YH001, envafolimab and doxorubicin in the common sarcoma ...

4. biocytogen.com biocytogen.com/first-patient-dosed-in-phase-1-2-trial-evaluating-yh001-in-combination-with-envafolimab-and-doxorubicin-in-front-line-sarcoma-patients

First Patient Dosed in Phase 1/2 Trial Evaluating YH001 ... The Phase 1/2 trial will assess the safety and efficacy of the triplet combination of YH001, envafolimab and doxorubicin in the common sarcoma subtypes.

5. mayo.edu mayo.edu/research/clinical-trials/cls-20547684

YH001 Plus Envafolimab With or Without Doxorubicin in ... The purpose of this study is to evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of YH001 when given with envafolimab ...

6. withpower.com withpower.com/trial/phase-2-soft-tissue-sarcoma-sts-9-2022-0c6e6

YH001 + Envafolimab for Sarcoma · Info for Participants While both treatments had manageable safety profiles, serious treatment-related adverse events occurred in 19% of patients receiving nivolumab and 26% in those ...